The natural history of a genetic subtype of arrhythmogenic right ventricular cardiomyopathy caused by a p.S358L mutation in TMEM43

To determine the phenotype and natural history of a founder genetic subtype of autosomal dominant arrhythmogenic right ventricular cardiomyopathy (ARVC) caused by a p.S358L mutation in TMEM43. The age of onset of cardiac symptoms, clinical events and test abnormalities were studied in 412 subjects (258 affected and 154 unaffected), all of which occurred in affected males significantly earlier and more often than unaffected males. Affected males were hospitalized four times more often than affected females (p ≤ 0.0001) and died younger (p ≤ 0.001). The temporal sequence from symptoms onset to death was prolonged in affected females by 1–2 decades. The most prevalent electrocardiogram (ECG) manifestation was poor R wave progression (PRWP), with affected males twice as likely to develop PRWP as affected females (p ≤ 0.05). Left ventricular enlargement (LVE) occurred in 43% of affected subjects, with 11% fulfilling criteria for dilated cardiomyopathy. Ventricular ectopy on Holter monitor was common and occurred early: the most diagnostically useful clinical test. No symptom or test could rule out diagnosis. This ARVC subtype is a sex‐influenced lethal arrhythmogenic cardiomyopathy, with a unique ECG finding, LV dilatation, heart failure and early death, where molecular pre‐symptomatic diagnosis has the greatest clinical utility.     

Anti-Cyclic Citrullinated Peptide Antibodies in Patients with Juvenile Idiopathic Arthritis

The objectives were to determine the prevalence and clinical significance of anti-cyclic citrullinated peptide (anti-CCP) antibodies in patients with juvenile idiopathic arthritis (JIA). Anti-CCP antibodies were checked by ELISA in 68 children with JIA, 38 males and 30 females with mean age of 10.6 (±4.02) years and disease duration of 3.7 (±1.8) years. Thirty-eight (56%) patients had polyarticular disease, 20 (29%) patients had oligoarticular disease and 10 (15%) patients had systemic onset disease. All patients had their antinuclear antibodies (ANA), rheumatoid factor (RF) and ESR checked and x-rays performed to look for erosions. Results were compared to those of 20 healthy children, 14 children with juvenile systemic lupus erythematosus (JSLE) and 30 adults with rheumatoid arthritis (RA). Anti-CCP antibodies were positive in 14/68 (20.6%) patients with JIA, all had polyarticular-onset disease. All patients with positive anti-CCP antibodies had RF-positive polyarthritis. Anti-CCP antibodies were negative in all patients with oligoarticular-onset and systemic-onset disease including 2 patients with extended oligoarthritis. Anti-CCP antibodies were negative in healthy and JSLE controls but were positive in 20/30 (66.5%) adults with RA. Anti-CCP antibodies correlated significantly with joint erosions in patients with JIA (p?=?0.004) but no significant relation was found between anti-CCP antibodies and ANA positivity or raised ESR. These data confirm that anti-CCP antibodies are less prevalent in JIA than adult RA but are detectable in a significant proportion of RF-positive patients with polyarticular-onset JIA. The current study showed significant relation between anti-CCP positivity and erosive joint disease in JIA.     

The Production and Characterization of Novel Heavy-Chain Antibodies Against the Tandem Repeat Region of MUC1 Mucin

Camelidae are known to produce immunoglobulins (Igs) devoid of light chains and constant heavy-chain domains (CH₁). Antigen-specific fragments of these heavy-chain IgGs (VHH) are of great interest in biotechnology applications. This paper describes the first example of successfully raised heavy-chain antibodies in Camelus dromedarius (single-humped camel) and Camelus bactrianus (two-humped camel) against a MUC1 related peptide that is found to be an important epitope expressed in cancerous tissue. Camels were immunized against a synthetic peptide corresponding to the tandem repeat region of MUC1 mucin and cancerous tissue preparation obtained from patients suffering from breast carcinoma. Three IgG subclasses with different binding properties to protein A and G were purified by affinity chromatography. Both conventional and heavy-chain IgG antibodies were produced in response to MUC1-related peptide. The elicited antibodies could react specifically with the tandem repeat region of MUC1 mucin in an enzyme linked immunosorbant assay (ELISA). Anti-peptide antibodies were purified after passing antiserum over two affinity chromatography columns. Using ELISA, immunocytochemistry and Western blotting, the interaction of purified antibodies with different antigens was evaluated. The antibodies were observed to be selectively bound to antigens namely: MUC1 peptide (tandem repeat region), human milk fat globule membrane (HMFG), deglycosylated human milk fat globule membrane (D-HMFG), homogenized cancerous breast tissue and a native MUC1 purified from ascitic fluid. K_a values of specific polyclonal anti-peptide antibodies were estimated in C. dromedarius and C. bactrianus, as 7 × 10¹⁰ M^{? 1} and 1.4 × 10¹⁰ M^{? 1} respectively.     

Development of a new bisphenol A electrochemical sensor based on a cadmium(ii) porphyrin modified carbon paste electrode

In this study, the (5,10,15,20-tetrakis[(4-methoxyphenyl)]porphyrinato)cadmium(ii) complex ([Cd(TMPP)]) was successfully used as a modifier in a carbon paste electrode (CPE) and exploited for bisphenol A (BPA) detection. Analytical performance revealed two linear ranges from 0.0015–15 μM and 0.015–1.5 mM with a detection limit of 13.5 pM. The proposed method was implemented in water samples, which resulted in quantitative signals over the range 6.5–1000 μM with recoveries between 92.6 and 107.7% for tap water and between 96.6 to 106.0% for mineral water.

In this study, the (5,10,15,20-tetrakis[(4-methoxyphenyl)]porphyrinato)cadmium(ii) complex ([Cd(TMPP)]) was successfully used as a modifier in a carbon paste electrode (CPE) and exploited for bisphenol A (BPA) detection.     

Outcome of endoscopic sphincterotomy in post cholecystectomy patients with sphincter of Oddi dysfunction as predicted by manometry and quantitative choledochoscintigraphy

BACKGROUND: Sphincter of Oddi dysfunction is diagnosed at manometry and, after cholecystectomy, non-invasively at quantitative choledochoscintigraphy. Patients may benefit from endoscopic sphincterotomy. AIMS: The aim of this study was to assess the usefulness of choledochoscintigraphy compared with manometry in predicting outcome of sphincterotomy in post cholecystectomy patients with sphincter of Oddi dysfunction. PATIENTS AND METHODS: Thirty patients with biliary-type pain complying with the Rome diagnostic criteria of sphincter of Oddi dysfunction and belonging to biliary group I and II were subjected to clinical evaluation, choledochoscintigraphic assessment of the hepatic hilum-duodenum transit time, endoscopic retrograde cholangiopancreatography, and perendoscopic manometry. Twenty two biliary group I and II patients with prolonged hepatic hilum-duodenum transit times were invited to undergo sphincterotomy. Fourteen patients underwent sphincterotomy; eight refused. Clinical and scintigraphic assessments were performed at follow up. RESULTS: Hepatic hilum-duodenum transit time was delayed in all patients with manometric evidence of sphincter of Oddi dysfunction, in all biliary group I patients and in 64% of biliary group II patients. At follow up, all patients who underwent sphincterotomy were symptom free and hepatic hilum-duodenum transit time had either normalised or significantly improved. A favourable post sphincterotomy outcome was predicted in 93% of cases at choledochoscintigraphy and in 57% at manometry. CONCLUSIONS: Quantitative choledochoscintigraphy is a useful and non-invasive test to diagnose sphincter of Oddi dysfunction as well as a reliable predictor of sphincterotomy outcome in post cholecystectomy biliary group I and II patients, irrespective of clinical classification and manometric findings.     

Ultra-fast,low dose high-pitch (FLASH) versus prospectively-gated coronary computed tomography angiography: Comparison of image quality and patient radiation exposure

Background

Coronary computed tomography angiography (CCTA) is increasingly being used for the evaluation of coronary artery disease; however, radiation exposure remains a major limitation of its use.

Enterococcal endocarditis: 107 cases from the international collaboration on endocarditis merged database

PURPOSE: To describe clinical features and outcomes of enterococcal left-sided native valve endocarditis and to compare it to endocarditis caused by other pathogens. SUBJECTS AND METHODS: Patients in the International Collaboration on Endocarditis-Merged Database were included if they had left-sided native valve endocarditis. Demographic characteristics, clinical features, and outcomes were analyzed. Multivariable analysis evaluated enterococcus as a predictor of mortality. RESULTS: Of 1285 patients with left-sided native valve endocarditis, 107 had enterococcal endocarditis. Enterococcal endocarditis was most frequently seen in elderly men, frequently involved the aortic valve, tended to produce heart failure rather than embolic events, and had relatively low short-term mortality. Compared to patients with non-enterococcal endocarditis, patients with enterococcal endocarditis had similar rates of nosocomial acquisition, heart failure, embolization, surgery, and mortality. Compared to patients with streptococcal endocarditis, patients with enterococcal endocarditis were more likely to be nosocomially acquired (9 of 59 [15%] vs 2 of 400 [1%]; P <.0001) and have heart failure (49 of 107 [46%] vs 234 of 666 [35%]; P = 0.03). Compared to patients with S. aureus endocarditis, patients with enterococcal endocarditis were less likely to embolize (28 of 107 [26%] vs 155 of 314 [49%]; P <.0001) and less likely to die (12 of 107 [11%] vs 83 of 313 [27%]; P = 0.001). Multivariable analysis of all patients with left-sided native valve endocarditis showed that enterococcal endocarditis was associated with lower mortality (odds ratio [OR] 0.49; 95% confidence interval [CI] 0.24 to 0.97). CONCLUSIONS: Enterococcal native valve endocarditis has a distinctive clinical picture with a good prognosis.